Cyclosporine A is the active ingredient in Restasis®, a drug that is used to treat dry eye disease. Cyclosporin A is poorly soluble in water, and so is currently formulated either by dissolving the drug in oil to form an emulsion, or by mixing the drug with high levels of surfactants and/or solubilizers to form an aqueous solution. The inventors have discovered a formulation of cyclosporin A using a new crystalline polymorph of cyclosporin A, to create nanosuspensions comprising particles of cyclosporin A having an average size of around 1 micrometer or less (to put that number in perspective, the average thickness of a human hair is around 100 micrometers).
A nanosuspension of cyclosporin A, when delivered topically to the eye, may have one or more advantages, including the following:
a higher bioavailability compared to suspensions, due to the higher surface area available for dissolution;
a longer retention on the eye due to smaller particles, leading to further improvement in bioavailability;
a lower potential for foreign body sensation or particle irritation, thus reducing tearing and drainage of formulations from the eye;
a lower level of surfactants or solubilizers in the formulation, improving tolerability and bioavailability of the drug.